Project Summary ? Core 2 Susceptibility to alcoholism has a clear genetic component. The VCU-ARC and its collaborators seeks to better understand ethanol-responsive genes by studying cross-species genetic correlates. These efforts have generated several ethanol-responsive gene candidates such as Clic4, GSK3B, and slo1. The Rodent Behavioral Core (Core 2) will expand these efforts by studying the consequences of manipulating these (and newly identified) candidate genes in a rodent behavioral battery that models specific aspects of acute ethanol sensitivity, consumption, and seeking behavior. Core 2 will use conditional genetically modified mice or viral transgene delivery to mouse or rat brain. Core 2 may also use environmental modulations to investigate gene x environment interactions on ethanol response behaviors. The intent of Core 2 is to correlate expression levels of an ethanol-responsive candidate gene to a particular behavioral outcome in order to gain a deeper understanding of the genetic basis of alcoholism. The results of Core 2 will provide valuable insight into the genetic basis of the complex behavioral and neurobiological adaptations that develop as a consequence of either acute or repeated ethanol exposure. This new knowledge will aid in the development of interventions for the prevention and/or treatment of ethanol abuse and alcoholism.